In mammalian cells, there are six members of the mixed lineage leukemia (MLL) family methyltransferases responsible for methylation of histone H3 lysine 4 (H3K4), including MLL1, MLL2, MLL3, MLL4, SET1A, and SET1B (Rao and Dou, 2015).Although originating from the same ancestor Set1 in yeast, MLL proteins play non-redundant roles in cells because the …
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After its translation, wild-type MLL1 is proteolytically cleaved by the enzyme taspase-1 (19, 20).The resulting 320-kDa N-terminal fragment (MLL-N) contains all domains except the transcriptional activation domain and the SET domain, both of which are retained by the 180-kDa C-terminal fragment (MLL-C).MLL-N and MLL-C normally associate with one …
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Taspase 1 mediates the cleavage of the MLL protein generating 320 kDa N-terminal (MLL-N) and 180 kDa C-terminal (MLL-C) fragments which then together dimerize in a large molecular weight complex [34,92,94,112,113].The MLL-C core complex that mediates H3K4 methylation consists of WD repeat-containing protein 5 (WDR5), ash2 (absent, small, or homeotic)-like (Drosophila) …
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Given the evidence that inhibition of NF-κB can severely limit MLL-AF9 leukemogenesis (Kuo et al., 2013), and is known to play a pro-survival or LSC-maintenance role in AML with diverse cytogenetics (Guzman et al., 2001; Kagoya et al., 2014), it is likely that this defect contributes to reduced survival of Mll1;Mll2 knockout MLL-AF9 cells.
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